State Dependent Beta Oscillations in the Cortico-Basal Ganglia Circuit and their Neuromodulation under Phase-Locked Inputs

<jats:title>Abstract</jats:title><jats:p>State-of-the-art therapeutic brain stimulation strategies are delivered open loop, using fixed parameters. However, brain states exhibit spontaneous fluctuations dependent upon different behavioural or disease states. Here, we use a model of the cortico-basal ganglia-thalamic circuit to demonstrate how connectivity underpins changes in subcortical beta oscillations – a commonly used control parameter for deep brain stimulation in Parkinson’s disease. We show that recurrent cortical-subcortical loops involving either the cortico-subthalamic or pallido-subthalamic pathways can act in antagonism to modulate the expression of beta band activity (14-30 Hz). These pathways alter the relative timing of intermittent activity across the network, with increased pallido-subthalamic connectivity increasing the propensity of the circuit to enter a state of autonomous oscillation. We demonstrate that phase-locked stimulation can modulate these oscillations, with an efficacy that ultimately depends upon the connectivity across the circuit. This work outlines critical factors required to implement state-adaptive closed-loop brain stimulation.</jats:p><jats:sec><jats:title>Highlights</jats:title><jats:list list-type="bullet"><jats:list-item><jats:p>Converging inputs to the subthalamic nucleus arriving via the external segment of globus pallidus and cortex act in antagonism and promote different beta rhythms.</jats:p></jats:list-item><jats:list-item><jats:p>Phase locked stimulation has the capacity to selectively enhance or suppress a brain rhythm depending on the stimulation timing.</jats:p></jats:list-item><jats:list-item><jats:p>The efficacy of stimulation and the parameters required to deliver it, e.g. stimulation timing, effective sensing and stimulation locations, are functions of network state.</jats:p></jats:list-item></jats:list></jats:sec>